Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants
| Autor: | Isabelle Coiffec, Vincent Lavoué, Andreas Kortenkamp, Bernard Jégou, Séverine Mazaud-Guittot, Laurianne Lesné, Martin Scholze, Nathalie Dejucq-Rainsford, Pierre Gaudriault |
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| Přispěvatelé: | Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES), CHEMIX-EST-12-171, ChemPSy-EST-13-081, Institut National de la Santé et de la Recherche Médicale (Inserm)., Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Pediatrics Health Toxicology and Mutagenesis MEDLINE Endocrine Disruptors 010501 environmental sciences urologic and male genital diseases 01 natural sciences Fetal Development 03 medical and health sciences Obstetrics and gynaecology Testis Pediatric surgery medicine Humans Endocrine system Pesticides Cells Cultured Stipend 0105 earth and related environmental sciences Gynecology business.industry Research Public Health Environmental and Occupational Health 3. Good health 030104 developmental biology Pharmaceutical Preparations 13. Climate action Human fetal Androgens Environmental Pollutants [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie business |
| Zdroj: | Environmental Health Perspectives Environmental Health Perspectives, National Institute of Environmental Health Sciences, 2017, 125 (8), pp.087004. ⟨10.1289/EHP1014⟩ Environmental Health Perspectives, 2017, 125 (8), pp.087004. ⟨10.1289/EHP1014⟩ |
| ISSN: | 1552-9924 0091-6765 |
| DOI: | 10.1289/ehp1014 |
| Popis: | Reproduced with permission from Environmental Health Perspectives Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. We thank all the staff of the Department of Obstetrics and Gynecology and the Department of Pediatric Surgery of the Rennes Sud Hospital (Rennes, France) and the participating women, without whom this study would not have been possible. We acknowledge the financial supports from the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES) ; CHEMIX-EST-12-171, ChemPSy- EST-13-081, Institut National de la Santé et de la Recherche Médicale (Inserm). P.Gaudriault is a recipient of a stipend of the Fondation pour la Recherche Médicale. |
| Databáze: | OpenAIRE |
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